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• W4386708630 abstract "Abstract Maintaining proper mother-daughter centriole engagement is crucial for controlling centrosome numbers and ensuring accurate cell division in both mitosis and meiosis. However, the mechanism responsible for this maintenance remains unclear. Here, we report that the Drosophila homolog of human ciliopathy gene Alström Syndrome 1 (Alms1) is required for maintaining centriole engagement during spermatocyte meiosis. We demonstrated that deletion of Alms1 results in premature centriole disengagement in prophase of meiosis I, leading to the formation of multipolar spindles and abnormal cell division in Drosophila spermatocytes. Further studies reveal that Alms1 localizes to the proximal centrioles, and functions downstream of cartwheel protein Sas-6 to regulate centriole engagement, and its highly conserved ALMS motif is required for Alms1’s function in centriole engagement. Moreover, we show that the centriole size and pericentriolar materials (PCM) have antagonistic roles on maintaining centriole engagement in alms1 mutant flies. Our findings highlight the critical role of Alms1 as a “glue protein” in maintaining mother-daughter centriole pair cohesion, potentially advancing our comprehension of the pathogenesis of Alström Syndrome. Significance statement Alström syndrome (AS) is a human ciliopathy that results from mutations in the ALMS1 gene inherited in an autosomal recessive manner. Elucidating the roles of ALMS1 and the underlying molecular mechanisms of AS is of paramount importance. In this study, using Drosophila model, we discovered that ALMS1 is localized at the proximal centrioles, and is crucial for the proper centriole engagement, spindle polarity, cell division in spermatocytes. Our findings reveal the new role of ALSM1 in maintaining centriole engagement, and suggest that non-ciliary function of ALMS1 may contribute to the pathogenesis of Alström Syndrome, warranting further investigation." @default.
• W4386708630 created "2023-09-14" @default.
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• W4386708630 date "2023-09-13" @default.
• W4386708630 modified "2023-10-01" @default.
• W4386708630 title "Alstrom Syndrome protein Alms1 is required for maintaining meiotic centriole engagement in spermatocytes of Drosophila" @default.
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• W4386708630 doi "https://doi.org/10.1101/2023.09.12.557481" @default.
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